• Maximum tolerated dose [ Designated as safety issue: Yes ]
• Dose-limiting toxicity [ Designated as safety issue: Yes ]
• Pharmacokinetics [ Designated as safety issue: No ]
• Radiographic response rate [ Designated as safety issue: No ]

• Maximum tolerated dose
• Dose-limiting toxicity
• Pharmacokinetics
• Radiographic response rate

• Survival [ Designated as safety issue: No ]
• Toxicity [ Designated as safety issue: Yes ]

• Survival
• Toxicity

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I/II trial is studying the side effects and best dose of oxaliplatin in treating patients with newly diagnosed glioblastoma multiforme.

OBJECTIVES:

• Determine the maximum tolerated dose of oxaliplatin in patients with newly diagnosed glioblastoma multiforme who are receiving or not receiving anticonvulsants known to be metabolized by P450.
• Determine the dose-limiting toxicity and safety profile of this drug in this patient population.
• Assess the pharmacokinetics of this drug on this schedule and determine the effects of P450-inducing anticonvulsants on the pharmacokinetics in these patients.
• Determine the radiographic response rate in patients treated with this drug.
• Determine survival and drug toxicity in these patients.

OUTLINE: This is a phase I dose-escalation study of oxaliplatin followed by a phase II study. Patients are stratified according to whether concurrent anticonvulsant drugs induce P450 (yes vs modest/no or no drugs).

• Phase I: Patients receive oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for a maximum of 6 courses in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients (per stratum) receive escalating doses of oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive oxaliplatin as in phase I at the MTD determined in phase I.

Patients are followed at 1 month, every 2 months until disease progression, and then monthly thereafter.

PROJECTED ACCRUAL: Approximately 24 patients (12 per stratum) will be accrued for the phase I part of this study within 8-12 months. A total of 18-35 patients will be accrued for the phase II part of this study within 5-12 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed supratentorial grade IV astrocytoma

  • Glioblastoma multiforme
• Subtotal resection or biopsy with measurable and contrast-enhancing disease on the postoperative, pretreatment MRI/CT scan

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL

Hepatic:

• Bilirubin normal

Renal:

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No serious concurrent infection or medical illness that would jeopardize ability to receive protocol chemotherapy with reasonable safety
• No other prior malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer
• No grade 2 or greater pre-existing sensory neuropathy
• No history of allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with protocol chemotherapy
• Mini mental score at least 15

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior immunotherapy for glioblastoma multiforme

• No prior biologic therapy for glioblastoma multiforme, including:

  • Immunotoxins
  • Immunoconjugates
  • Antiangiogenesis compounds
  • Antisense
  • Peptide receptor antagonists
  • Interferons
  • Interleukins
  • Tumor infiltrating lymphocytes
  • Lymphokine activated killer cells
  • Gene therapy
• No concurrent filgrastim (G-CSF)

Chemotherapy:

• No prior chemotherapy for glioblastoma multiforme

Endocrine therapy:

• No prior hormonal therapy for glioblastoma multiforme
• Prior glucocorticoid therapy for glioblastoma multiforme allowed
• Must be maintained on a stable (lowest required dose) corticosteroid regimen for at least 5 days before and during study
• No concurrent dexamethasone as an antiemetic

Radiotherapy:

• No prior radiotherapy for glioblastoma multiforme

Surgery:

• See Disease Characteristics
• Recovered from immediate postoperative period

Other:

• At least 10 days since prior anticonvulsant drug that induces hepatic metabolic enzymes
• No other concurrent investigational agents